Prevalence of polypharmacy in pregnancy: a systematic review

Objectives The use of medications among pregnant women has been rising over the past few decades but the reporting of polypharmacy has been sporadic. The objective of this review is to identify literature reporting the prevalence of polypharmacy among pregnant women, the prevalence of multimorbidity in women taking multiple medications in pregnancy and associated effects on maternal and offspring outcomes. Design MEDLINE and Embase were searched from their inception to 14 September 2021 for interventional trials, observational studies and systematic reviews reporting on the prevalence of polypharmacy or the use of multiple medications in pregnancy were included. Data on prevalence of polypharmacy, prevalence of multimorbidity, combinations of medications and pregnancy and offspring outcomes were extracted. A descriptive analysis was performed. Results Fourteen studies met the review criteria. The prevalence of women being prescribed two or more medications during pregnancy ranged from 4.9% (4.3%–5.5%) to 62.4% (61.3%–63.5%), with a median of 22.5%. For the first trimester, prevalence ranged from 4.9% (4.7%–5.14%) to 33.7% (32.2%–35.1%). No study reported on the prevalence of multimorbidity, or associated pregnancy outcomes in women exposed to polypharmacy. Conclusion There is a significant burden of polypharmacy among pregnant women. There is a need for evidence on the combinations of medications prescribed in pregnancy, how this specifically affects women with multiple long-term conditions and the associated benefits and harms. Tweetable abstract Our systematic review shows significant burden of polypharmacy in pregnancy but outcomes for women and offspring are unknown. PROSPERO registration number CRD42021223966.


Introduction
Objectives 4 Provide an explicit statement of the objective(s) or question(s) the review addresses. Introduction

METHODS
Eligibility criteria 5 Specify the inclusion and exclusion criteria for the review and how studies were grouped for the syntheses.
Methodseligibility criteria Information sources 6 Specify all databases, registers, websites, organisations, reference lists and other sources searched or consulted to identify studies. Specify the date when each source was last searched or consulted.
Methodssearch strategy Search strategy 7 Present the full search strategies for all databases, registers and websites, including any filters and limits used. Methodssearch strategy, Appendix S1 Selection process 8 Specify the methods used to decide whether a study met the inclusion criteria of the review, including how many reviewers screened each record and each report retrieved, whether they worked independently, and if applicable, details of automation tools used in the process.
Methods -study selection and data abstraction, author contribution Data collection process 9 Specify the methods used to collect data from reports, including how many reviewers collected data from each report, whether they worked independently, any processes for obtaining or confirming data from study investigators, and if applicable, details of automation tools used in the process. Methods -study selection and data abstraction, author contribution Data items 10a List and define all outcomes for which data were sought. Specify whether all results that were compatible with each outcome domain in each study were sought (e.g., for all measures, time points, analyses), and if not, the methods used to decide which results to collect.
Methods -study selection and data abstraction, outcome measurement 10b List and define all other variables for which data were sought (e.g., participant and intervention characteristics, funding sources).
Describe any assumptions made about any missing or unclear information.
Methods -study selection and data BMJ Publishing Group Limited (BMJ) disclaims all liability and responsibility arising from any reliance Study risk of bias assessment 11 Specify the methods used to assess risk of bias in the included studies, including details of the tool(s) used, how many reviewers assessed each study and whether they worked independently, and if applicable, details of automation tools used in the process.

Methods -study selection and data abstraction
Effect measures 12 Specify for each outcome the effect measure(s) (e.g., risk ratio, mean difference) used in the synthesis or presentation of results. Methodsoutcome measurement Synthesis methods 13a Describe the processes used to decide which studies were eligible for each synthesis (e.g., tabulating the study intervention characteristics and comparing against the planned groups for each synthesis (item #5)).
Methods -study selection and data abstraction and summary measures and results synthesis 13b Describe any methods required to prepare the data for presentation or synthesis, such as handling of missing summary statistics, or data conversions.

Methods -summary measures and results synthesis
13c Describe any methods used to tabulate or visually display results of individual studies and syntheses. Methods -summary measures and results synthesis 13d Describe any methods used to synthesize results and provide a rationale for the choice(s). If meta-analysis was performed, describe the model(s), method(s) to identify the presence and extent of statistical heterogeneity, and software package(s) used.

Methods -summary measures and results synthesis
13e Describe any methods used to explore possible causes of heterogeneity among study results (e.g., subgroup analysis, metaregression).
N/a 13f Describe any sensitivity analyses conducted to assess robustness of the synthesized results. N/a Reporting bias assessment 14 Describe any methods used to assess risk of bias due to missing results in a synthesis (arising from reporting biases). Methods -study selection and data abstraction (risk of bias) Certainty assessment 15 Describe any methods used to assess certainty (or confidence) in the body of evidence for an outcome. Methods -study selection and data abstraction (risk of bias)

RESULTS
Study selection 16a Describe the results of the search and selection process, from the number of records identified in the search to the number of studies included in the review, ideally using a flow diagram.  Checklist item Location where item is reported 16b Cite studies that might appear to meet the inclusion criteria, but which were excluded, and explain why they were excluded.
Results, references Study characteristics 17 Cite each included study and present its characteristics. Results, Table s1 Risk of bias in studies 18 Present assessments of risk of bias for each included study.

Yes
Synthesis of results 8 Present results for main outcomes, preferably indicating the number of included studies and participants for each. If meta-analysis was done, report the summary estimate and confidence/credible interval. If comparing groups, indicate the direction of the effect (i.e. which group is favoured).

DISCUSSION
Limitations of evidence 9 Provide a brief summary of the limitations of the evidence included in the review (e.g. study risk of bias, inconsistency and imprecision).

Yes
Interpretation 10 Provide a general interpretation of the results and important implications. Yes OTHER Funding 11 Specify the primary source of funding for the review. Yes Registration 12 Provide the register name and registration number. Prospero protocol cited in methods and references BMJ Publishing Group Limited (BMJ) disclaims all liability and responsibility arising from any reliance Supplemental material placed on this supplemental material which has been supplied by the author(s)